吳華林教授(特聘)

  • Prof. H.L. Wu

    分機: 5541 (研究室) 5524 (實驗室); Email

    美國俄亥俄州立大學博士

    研究方向：

    心臟血管疾病之研究、蛋白生物科技

    研究興趣：

  • 人類凝血(酉+每)調節素（Thrombomodulin, TM）利用基因重組的方法，構築不同的 TM 片段及 TM 突變基因，並在細胞內表現。再利用共軛焦雷射顯微鏡觀察不同區域的 TM 對細胞外型、細胞間交互作用、細胞移行及細胞增生的影響，並分析 TM 在細胞內的分佈與探討其可能的生理意義。此外，亦探討 TM 調控癌細胞增生與轉移，和所參與的訊息傳遞途徑。

  • 人類血管靜止蛋白（angiostatin）之新功能研究。利用基因工程及蛋白質表現與純化技術製備多種 angiostatin 突變株，並在細胞及動物模式等層面，來研究 kringle 的結構與血管內皮細胞生長及抑制血管新生等功能的關係，並尋找效果更顯著之蛋白株。

  • 血管生物學之研究。此部分為追求卓越計畫之主題，以研究動脈粥狀硬化(atherosclerosis)為主。我們探討與動脈粥狀硬化相關之基因表現、基因多型性與疾病之相關性。並研究新發現之內皮細胞相關基因，如 endosialin，對血管功能的影響。

    • Selected publications:

  • Li YH, Chung HC, Luo CY, Chao TH, Shyu KG, Shi GY, Wu HL. (2010) Thrombomodulin is upregulated in cardiomyocytes during cardiac hypertrophy and prevents the progression of contractile dysfunction. J Card Fail. 2010 Dec;16(12):980-90. [Abstract]

  • Kao YC, Wu LW, Shi CS, Chu CH, Huang CW, Kuo CP, Sheu HM, Shi GY, Wu HL. (2010) Downregulation of thrombomodulin, a novel target of Snail, induces tumorigenesis through epithelial-mesenchymal transition. Mol Cell Biol. 2010 Oct;30(20):4767-85. Epub 2010 Aug 16. [Abstract]

  • Lin YD, Yeh ML, Yang YJ, Tsai DC, Chu TY, Shih YY, Chang MY, Liu YW, Tang AC, Chen TY, Luo CY, Chang KC, Chen JH, Wu HL, Hung TK, Hsieh PC. (2010) Intramyocardial peptide nanofiber injection improves postinfarction ventricular remodeling and efficacy of bone marrow cell therapy in pigs. Circulation. 2010 Sep 14;122(11 Suppl):S132-41. [Abstract]

  • Su YD, Chiu KC, Chang NS, Wu HL, Chen SJ. (2010) Study of cell-biosubstrate contacts via surface plasmon polariton phase microscopy. Opt Express. 2010 Sep 13;18(19):20125-35. doi: 10.1364/OE.18.020125. [Abstract]

  • Chan SS, Shueh YZ, Bustamante N, Tsai SJ, Wu HL, Chen JH, Hsieh PC. (2010) Genetic fate-mapping for studying adult cardiomyocyte replenishment after myocardial injury. Methods Mol Biol. 2010;660:201-11. [Abstract]

  • Lin CN, Kao CY, Miao CH, Hamaguchi N, Wu HL, Shi GY, Liu YL, High KA, Lin SW. (2010) Generation of a novel factor IX with augmented clotting activities in vitro and in vivo. J Thromb Haemost. 2010 Aug;8(8):1773-83. doi: 10.1111/j.1538-7836.2010.03913.x. Epub 2010 May 21. [Abstract]

  • Kao CY, Lin CN, Yu IS, Tao MH, Wu HL, Shi GY, Yang YL, Kao JT, Lin SW. (2010) FIX-Triple, a gain-of-function factor IX variant, improves haemostasis in mouse models without increased risk of thrombosis. Thromb Haemost. 2010 Aug 2;104(2):355-65. Epub 2010 Jun 10. [Abstract]

  • Liu HC, Eng HL, Yang YF, Wang YH, Lin KT, Wu HL, Lin TM. (2010) Aberrant RNA splicing in RHD 7-9 exons of DEL individuals in Taiwan: a mechanism study. Biochim Biophys Acta. 2010 Jun;1800(6):565-73. Epub 2010 Feb 25. [Abstract]

  • He RY, Lin CY, Su YD, Chiu KC, Chang NS, Wu HL, Chen SJ. (2010) Imaging live cell membranes via surface plasmon-enhanced fluorescence and phase microscopy. Opt Express. 2010 Feb 15;18(4):3649-59. doi: 10.1364/OE.18.003649. [Abstract]

  • Chang PC, Wu HL, Lin HC, Wang KC, Shi GY. (2010) Human plasminogen kringle 1-5 reduces atherosclerosis and neointima formation in mice by suppressing the inflammatory signaling pathway. J Thromb Haemost. 2010 Jan;8(1):194-201. Epub 2009 Oct 30. [Abstract]

  • Wang SH, Lin SJ, Chen YH, Lin FY, Shih JC, Wu CC, Wu HL, Chen YL. (2009) Late outgrowth endothelial cells derived from Wharton jelly in human umbilical cord reduce neointimal formation after vascular injury: involvement of pigment epithelium-derived factor. Arterioscler Thromb Vasc Biol. 2009 Jun;29(6):816-22. Epub 2009 Apr 2. [Abstract]

  • Lo IC, Lin TM, Chou LH, Liu SL, Wu LW, Shi GY, Wu HL, Jiang MJ. (2009) Ets-1 mediates platelet-derived growth factor-BB-induced thrombomodulin expression in human vascular smooth muscle cells. Cardiovasc Res. 2009 Mar 1;81(4):771-9. Epub 2008 Dec 17. [Abstract]

  • Kao TT, Chang WN, Wu HL, Shi GY, Fu TF. (2009) Recombinant zebrafish {gamma}-glutamyl hydrolase exhibits properties and catalytic activities comparable with those of mammalian enzyme. Drug Metab Dispos. 2009 Feb;37(2):302-9. Epub 2008 Nov 12. [Abstract]

  • Chen YH, Huang YH, Wu HL, Wu MP, Chang WT, Kuo YZ, Lu KC, Wu LW. (2008) Angiostatin K1-3 induces E-selectin via AP1 and Ets1: a mediator for anti-angiogenic action of K1-3. J Thromb Haemost. 2008 Nov;6(11):1953-61. Epub 2008 Aug 28. [Abstract]

  • Shi CS, Shi GY, Hsiao SM, Kao YC, Kuo KL, Ma CY, Kuo CH, Chang BI, Chang CF, Lin CH, Wong CH, Wu HL. (2008) Lectin-like domain of thrombomodulin binds to its specific ligand Lewis Y antigen and neutralizes lipopolysaccharide-induced inflammatory response. Blood. 2008 Nov 1;112(9):3661-70. Epub 2008 Aug 18. [Abstract]

  • Liu PY, Lin CC, Tsai WC, Li YH, Lin LJ, Shi GY, Hong JS, Chen JH, Wu HL. (2008) Treatment with dextromethorphan improves endothelial function, inflammation and oxidative stress in male heavy smokers. J Thromb Haemost. 2008 Oct;6(10):1685-92. Epub 2008 Jul 18. [Abstract]

  • Lin TM, Chen CH, Wu HL, Wang CH, Chen YL, Eng HL. (2008) The association of C (-260)-->T polymorphism in CD14 promoter and Chlamydia pneumoniae infection in ischemic stroke patients. Am J Clin Pathol. 2008 Oct;130(4):595-601. [Abstract]

  • Chang PC, Chang YJ, Wu HL, Chang CW, Lin CI, Wang WC, Shi GY. (2008) Mutation of human plasminogen kringle 1-5 enhances anti-angiogenic action via increased interaction with integrin alpha(v)beta(3). Thromb Haemost. 2008 Apr;99(4):729-38. [Abstract]

  • Kao TT, Wang KC, Chang WN, Lin CY, Chen BH, Wu HL, Shi GY, Tsai JN, Fu TF. (2008) Characterization and comparative studies of zebrafish and human recombinant dihydrofolate reductases--inhibition by folic acid and polyphenols. Drug Metab Dispos. 2008 Mar;36(3):508-16. Epub 2007 Dec 3.[Abstract]

  • Wu HL, Lin CI, Huang YL, Chen PS, Kuo CH, Chen MS, Wu GC, Shi GY, Yang HY, Lee H. (2008) Lysophosphatidic acid stimulates thrombomodulin lectin-like domain shedding in human endothelial cells. Biochem Biophys Res Commun. 2008 Feb 29;367(1):162-8. Epub 2007 Dec 31. [Abstract]

  • Li YH, Hsieh CY, Wang DL, Chung HC, Liu SL, Chao TH, Shi GY, Wu HL. (2007) Remodeling of carotid arteries is associated with increased expression of thrombomodulin in a mouse transverse aortic constriction model. Thromb Haemost. 2007 Apr;97(4):658-64. [Abstract]

  • Liu PY, Li YH, Chao TH, Wu HL, Lin LJ, Tsai LM, Chen JH. (2007) Synergistic effect of cytochrome P450 epoxygenase CYP2J2*7 polymorphism with smoking on the onset of premature myocardial infarction. Atherosclerosis. 2007 Nov;195(1):199-206. Epub 2006 Nov 28. [Abstract]

  • Shi CS, Huang HC, Wu HL, Kuo CH, Chang BI, Shiao MS, Shi GY. (2007) Salvianolic acid B modulates hemostasis properties of human umbilical vein endothelial cells. Thromb Res. 2007;119(6):769-75. Epub 2006 Jul 17 [Abstract]

  • Hsu HY, Wu HL, Tan SK, Li VP, Wang WT, Hsu J, Cheng CH. (2007) Geldanamycin interferes with the 90-kDa heat shock protein, affecting lipopolysaccharide-mediated interleukin-1 expression and apoptosis within macrophages. Mol Pharmacol. 2007 Jan;71(1):344-56. Epub 2006 Jul 25. [Abstract]

  • Liu SL, Li YH, Shi GY, Jiang MJ, Chang JH, Wu HL. (2007) The effect of statin on the aortic gene expression profiling. Int J Cardiol. 2007 Jan 2;114(1):71-7. Epub 2006 May 5. [Abstract]

  • Chiang AN, Wu HL, Yeh HI, Chu CS, Lin HC, Lee WC. (2006) Antioxidant effects of black rice extract through the induction of superoxide dismutase and catalase activities. Lipids. 2006 Aug;41(8):797-803. [Abstract]

  • He, R. -Y., Chang, G. -L., Wu, H. -L., Lin, C. -H., Chiu, K. -C., Su, Y. -D., and Chen, S. -J. (2006) Enhanced live cell membrane imaging using surface plasmon-enhanced total internal reflection fluorescence microscopy. Optics Express. 14, 9307-9316.

  • Liu SL, Li YH, Shi GY, Chen YH, Huang CW, Hong JS, Wu HL. (2006) A novel inhibitory effect of naloxone on macrophage activation and atherosclerosis formation in mice. J Am Coll Cardiol. 2006 Nov 7;48(9):1871-9. Epub 2006 Oct 17. [Abstract]

  • Liu PY, Li YH, Chan SH, Lin LJ, Wu HL, Shi GY, Chen JH. (2006) Genotype-phenotype association of matrix metalloproteinase-3 polymorphism and its synergistic effect with smoking on the occurrence of acute coronary syndrome. Am J Cardiol. 2006 Oct 15;98(8):1012-7. Epub 2006 Aug 22. [Abstract]

  • Liu PY, Li YH, Wu HL, Chao TH, Tsai LM, Lin LJ, Shi GY, Chen JH. (2006) Platelet-activating factor-acetylhydrolase A379V (exon 11) gene polymorphism is an independent and functional risk factor for premature myocardial infarction. J Thromb Haemost. 2006 May;4(5):1023-8. [Abstract]

  • Chen YH, Wu HL, Li C, Huang YH, Chiang CW, Wu MP, Wu LW. (2006) Anti-angiogenesis mediated by angiostatin K1-3, K1-4 and K1-4.5. Involvement of p53, FasL, AKT and mRNA deregulation. Thromb Haemost. 2006 Apr;95(4):668-77. [Abstract]

  • Li YH, Shi GY, Wu HL. (2006) The role of thrombomodulin in atherosclerosis: from bench to bedside. Cardiovasc Hematol Agents Med Chem. 2006 Apr;4(2):183-7. Review. [Abstract]

  • Liu PY, Li YH, Tsai WC, Tsai LM, Chao TH, Wu HL, Chen JH. (2005) Stromelysin-1 promoter 5A/6A polymorphism is an independent genetic prognostic risk factor and interacts with smoking cessation after index premature myocardial infarction. J Thromb Haemost. 2005 Sep;3(9):1998-2005. [Abstract]

  • Shi CS, Shi GY, Chang YS, Han HS, Kuo CH, Liu C, Huang HC, Chang YJ, Chen PS, Wu HL. (2005) Evidence of Human Thrombomodulin Domain as a Novel Angiogenic Factor. Circulation. 2005 Apr 5;111(13):1627-36. Epub 2005 Mar 28. [Abstract]

  • Lee H, Lin CI, Liao JJ, Lee YW, Yang HY, Lee CY, Hsu HY, Wu HL. (2004) Lysophospholipids increase ICAM-1 expression in HUVEC through a Gi- and NF-kappaB-dependent mechanism. Am J Physiol Cell Physiol. 2004 Dec;287(6):C1657-66. Epub 2004 Aug 4. [Abstract]

  • Jiang SJ, Lin TM, Shi GY, Eng HL, Chen HY, Wu HL. (2004) Inhibition of bovine herpesvirus-4 replication by arsenite through downregulation of the extracellular signal-regulated kinase signaling pathway. J Biomed Sci. 2004 Jul-Aug;11(4):500-10. [Abstract]

  • Yu IS, Lin SR, Huang CC, Tseng HY, Huang PH, Shi GY, Wu HL, Tang CL, Chu PH, Wang LH, Wu KK, Lin SW. (2004) TXAS-deleted mice exhibit normal thrombopoiesis, defective hemostasis, and resistance to arachidonate-induced death. Blood. 2004 Jul 1;104(1):135-42. Epub 2004 Mar 9. [Abstract]

  • Chao TH, Li YH, Chen JH, Wu HL, Shi GY, Tsai WC, Chen PS, Liu PY. (2004) Relation of thrombomodulin gene polymorphisms to acute myocardial infarction in patients Am J Cardiol. 2004 Jan 15;93(2):204-7. [Abstract]

  • Chen CH, Lo YK, Ke D, Liu CK, Liou CW, Wu HL, Lai ML; Southern Taiwan Young Stroke Study Group. (2004) Platelet glycoprotein Ia C807T, Ib C3550T, and IIIa Pl(A1/A2) polymorphisms and ischemic stroke in young Taiwanese. J Neurol Sci. 2004 Dec 15;227(1):1-5. [Abstract]

  • Jiang SJ, Lin TM, Shi GY, Eng HL, Chen HY, Wu HL. (2004) Inhibition of bovine herpesvirus-4 replication in endothelial cells by arsenite. Antiviral Res. 2004 Sep;63(3):167-75. [Abstract]

  • Chao TH, Li YH, Chen JH, Wu HL, Shi GY, Liu PY, Tsai WC, Guo HR. (2004) The 161TT genotype in the exon 6 of the peroxisome-proliferator-activated receptor gamma gene is associated with premature acute myocardial infarction and increased lipid peroxidation in habitual heavy smokers. Clin Sci (Lond). 2004 Nov;107(5):461-6. [Abstract]

  • Liu PY, Li YH, Tsai WC, Chao TH, Tsai LM, Wu HL, Chen JH. (2003) Prognostic value and the changes of plasma levels of secretory type II phospholipase A2 in patients with coronary artery disease undergoing percutaneous coronary intervention. Eur Heart J. 2003 Oct;24(20):1824-32.[Abstract]

  • Chang YJ, Wu HL, Hsu YC, Hamaguchi N, Shi GY, Shen MC, Lin SW. (2003) Discontinuous residues of factor IX constitute a surface for binding the anti-factor IX monoclonal antibody A-5. Thromb Res. 2003;111(4-5):293-9. [Abstract]

  • Huang HC, Shi GY, Jiang SJ, Shi CS, Wu CM, Yang HY, Wu HL. (2003) Thrombomodulin-mediated cell adhesion: involvement of its lectin-like domain. J Biol Chem. 2003 Nov 21;278(47):46750-9. Epub 2003 Sep 01. [Abstract]

  • Chen YH, Wu HL, Chen CK, Huang YH, Yang BC, Wu LW. (2003) Angiostatin antagonizes the action of VEGF-A in human endothelial cells via two distinct pathways. Biochem Biophys Res Commun. 2003 Oct 24;310(3):804-10. [Abstract]

  • Sumariwalla PF, Cao Y, Wu HL, Feldmann M, Paleolog EM. (2003) The angiogenesis inhibitor protease-activated kringles 1-5 reduces the severity of murine collagen-induced arthritis. Arthritis Res Ther. 2003;5(1):R32-9. Epub 2002 Oct 31. [Abstract]

  • Cheng PN, Chang TT, Jen CM, Ko AW, Young KC, Wu HL. (2003) Molecular evidence for transmission of GB virus-C/Hepatitis G virus infection within family: close relationship between mother and child. Hepatogastroenterology 2003 Jan-Feb;50(49):151-6 [Abstract]

  • Liu PY, Chen JH, Li YH, Wu HL, Shi GY. (2003) Synergistic effect of stromelysin-1 (matrix metallo-proteinase-3) promoter 5A/6A polymorphism with smoking on the onset of young acute myocardial infarction. Thromb Haemost. 2003 Jul;90(1):132-9. [Abstract]

  • Young KC, Lin PW, Hsiao WC, Chang TT, Chang YC, Wu HL. (2002) Variation of hepatitis C virus load, hypervariable region 1 quasispecies and CD81 hepatocyte expression in hepatocellular carcinoma and adjacent non-cancerous liver. J Med Virol 2002 Oct;68(2):188-96 [Abstract]

  • Chang YJ, Wu HL, Hamaguchi N, Hsu YC, Lin SW. (2002) Identification of functionally important residues of the epidermal growth factor-2 domain of factor IX by alanine-scanning mutagenesis. Residues Asn(89)-Gly(93) are critical for binding factor VIIIa. J Biol Chem 2002 Jul 12;277(28):25393-9 [Abstract]

  • Jiang SJ, Lin TM, Wu HL, Han HS, Shi GY. (2002) Decrease of fibrinolytic activity in human endothelial cells by arsenite. Thromb Res 2002 Jan 1;105(1):55-62 [Abstract]

  • Li YH, Chen JH, Tsai WC, Chao TH, Guo HR, Tsai LM, Wu HL, Shi GY. (2002) Synergistic effect of thrombomodulin promoter -33G/A polymorphism and smoking on the onset of acute myocardial infarction. Thromb Haemost 2002 Jan;87(1):86-91[Abstract]

  • Han HS, Yang SL, Yeh HY, Lin JC, Wu HL, Shi GY. (2001) Studies of a novel human thrombomodulin immobilized substrate: surface characterization and anticoagulation activity evaluation. J Biomater Sci Polym Ed 2001;12(10):1075-89 [Abstract]

  • Shieh SJ, Chiu HY, Shi GY, Wu CM, Wang JC, Chen CH, Wu HL. (2001) A novel platelet-rich arterial thrombosis model in rabbits. Simple, reproducible, and dynamic real-time measurement by using double-opposing inverted-sutures model. Thromb Res 2001 Sep 1;103(5):363-76 [Abstract]

  • Chang TT, Chang TY, Chen CC, Young KC, Roan JN, Lee YC, Cheng PN, Wu HL. (2001) Existence of hepatitis C virus in Culex quinquefasciatus after ingestion of infected blood: experimental approach to evaluating transmission by mosquitoes. Clin Microbiol 2001 Sep;39(9):3353-5 [Abstract]

  • Li YH, Chen CH, Yeh PS, Lin HJ, Chang BI, Lin JC, Guo HR, Wu HL, Shi GY, Lai ML, Chen JH. (2001) Functional mutation in the promoter region of thrombomodulin gene in relation to carotid atherosclerosis. Atherosclerosis 2001 Feb 15;154(3):713-9 [Abstract]

  • Li YH, Chen JH, Wu HL, Shi GY, Huang HC, Chao TH, Tsai WC, Tsai LM, Guo HR, Wu WS, Chen ZC. (2000) G-33A mutation in the promoter region of thrombomodulin gene and its association with coronary artery disease and plasma soluble thrombomodulin levels. Am J Cardiol 2000 Jan 1;85(1):8-12 [Abstract]

  • Cheng PN, Chang TT, Yang MH, Hu SC, Young KC, Wu HL, Jen CM, Ko AW, Lu SC. (2000) GB virus-C/hepatitis G virus infection in a hepatitis C virus endemic village: prevalence in residents with low educational attainment and frequent recovery in females. Liver 2000 Jun;20(3):222-7 [Abstract]

  • Lin TM, Jiang MJ, Eng HL, Shi GY, Lai LC, Huang BJ, Huang KY, Wu HL. (2000) Experimental infection with bovine herpesvirus-4 enhances atherosclerotic process in rabbits. Lab Invest 2000 Jan;80(1):3-11 [Abstract]

  • Lin TM, Shi GY, Jiang SJ, Tsai CF, Hwang BJ, Hsieh CT, Wu HL. (1999) Persistent infection of bovine herpesvirus type 4 in bovine endothelial cell cultures. Vet Microbiol 1999 Oct;70(1-2):41-53 [Abstract]

  • Lin MT, Su WC, Cheng ML, Cheng KS, Chang WC, Wing LH, Jen CJ, Wu HL. (1999) The various effects of fractionated oxidized low density lipoproteins on the growth of smooth muscle cells in culture. J Biomed Sci 1999 Jul-Aug;6(4):260-8 [Abstract]

  • Cao R, Wu HL, Veitonmaki N, Linden P, Farnebo J, Shi GY, Cao Y. (1999) Suppression of angiogenesis and tumor growth by the inhibitor K1-5 generated by plasmin-mediated proteolysis. Proc Natl Acad Sci U S A 1999 May 11;96(10):5728-33 [Abstract]

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    Updated: 17 Dec. 2010